Diabetic autonomic neuropathy (DAN) ostensibly facilitates malignant arrhythmias by altering electrical stability and/or impairing myocardial blood flow. Cardiac sympathetic deficits predict a poor prognosis with 5-year mortality approaching 60% and cardiorespiratory arrest secondary to autonomic denervation has been implicated in sudden death. The aims of this application are to evaluate whether diabetic patients with heterogeneous sympathetic innervation and parasympathetic denervation demonstrate paradoxical vascular responsiveness in the islands of preserved cardiac sympathetic innervation on sympathetic activation (cold pressor test) using PET and Nitrogen-13-ammonia. These studies will explore the pathophysiological significance of regional cardiac denervation in DAN and will serve as the basis on which to design animal and human studies in which the aim will be the development of therapeutic strategies for the prevention of sudden cardiac death.